Synthesis of derivatives of dicarbamates from reduction products of 2-hydroxymethyl-5-furufural (hmf)

ABSTRACT

Dicarbamates of the reduction products of 2-hydroxymethyl-5-furfural (HMF) and a method of preparing the same are described. The method involves reacting a mixture of an isohexide and a cynate salt in a non-aqueous solvent, with a miscible acid having a pKa of about 3.7 or less. The dicarbamates of HMF-reduction products can serve as precursor materials from which various derivative compounds can be synthesized.

BENEFIT OF PRIORITY

The present application claims benefit of priority of U.S. patentapplication Ser. No. 14/781,364, filed Sep. 20, 2015, which claimspriority from International Application No. PCT/US2014/037047, filed May7,2014, which claims priority from U.S. Provisional Application No.61/833,951, filed Jun. 12, 2013, the contents of each are hereinincorporated.

FIELD OF INVENTION

The present invention relates to a synthesis of precursor compounds forpolymers. In particular, the present invention pertains to a method forpreparing dicarbamates of the reduction products of2-hydroxymethyl-5-furfural (HMF) (i.e, furan-2,5-dimethanol (FDM) andbis(hydroxymethyl)-tetrahydrofuran (bHMTHF)), and derivative compoundsof such dicarbamates.

BACKGROUND

Traditionally, polymers and commodity chemicals have been prepared frompetroleum-derived feedstock. As petroleum supplies have becomeincreasingly costly and difficult to access, interest and research hasincreased to develop renewable or “green” alternative materials frombiologically-derived sources for chemicals that will serve ascommercially acceptable alternatives to conventional, petroleum-based or-derived counterparts, or for producing the same materials as producedfrom fossil, non-renewable sources.

Carbohydrates or sugars are ubiquitous in agricultural materials, andhence are rational precursors for empirical innovations in the “green”materials area. Organic compounds that are readily derived from sugarsinclude furans, robust cyclic ethers that possess structural featureswhich can be useful for making certain polymers, pharmaceuticals, orsolvents, among other industrial constituents.

A compound that has received considerable attention of late is5-(hydroxymethyl)furfural (HMF), (FIG. 1), a salient dehydration productof the abundant, inexpensive monosaccharide, fructose.

FIG. 1. Chemical Structure of HMF

HMF is a versatile chemical antecedent to various furanic ring-basedderivatives that are known intermediates for a multitude of chemicalsyntheses, and as plausible surrogates for aromatic hydrocarbons thatderive from petroleum resources. Due to HMF's diverse functionalities,some have proposed that HMF be used to produce a wide range ofcommodities such as polymers, solvents, surfactants, pharmaceuticals,and plant protection agents. As alternates, derivatives of HMF arecomparable to benzene-based aromatic compounds or to other compoundscontaining a furan or tetrahydrofuran (THF). HMF and 2,5-disubstitutedfurans and THF analogs, therefore, have great potential in the field ofintermediate chemicals from renewable agricultural resources.

HMF itself, however, is rather unsuitable as a chemical intermediatesubstrate, given its propensity to decompose under thermo-oxidativeconditions. Thus, one should look to derivatives of HMF for practicalcommercial utility. One derivative is furan-2,5-dimethanol (abbreviatedas FDM, Scheme 1), which is produced from partial hydrogenation(aldehyde reduction) of HMF.

Other derivatives are 2,5-bis(hydroxymethyl)tetrahydrofuran (abbreviatedas bHMTHF), saturated stereoisomeric analogs produced in a 9:1 cis(B):trans (C) diastereometic ratio when both the ring and aldehydemoieties of HMF are reduce completely (Scheme 2).

These materials can be of value as a molecular antecedent, for example,to polyesters, polyurethane foams, FDCA, plasticizers, additives,lubricants, and amphiphiles.

To become market competitive with petroleum products, however, thepreparation of HMF derivatives from standard agricultural raw materials,such as sugars, need to become economically feasible in terms of cost.Heretofore, research for chemical derivatives using FDM and/or bHMTHFshas received limited attention due in part to the great cost andrelative paucity (e.g., ˜$200 per gram commercially) of the compounds.Recently, a need has arisen for a way to unlock the potential of FDM andbHMTHFs and their derivative compounds, as these chemical entities havegained attention as valuable glycolic antecedents for the preparation ofpolymers, solvents, additives, lubricants, and plasticizers, etc.Furthermore, the inherent, immutable chirality of bHMTHFs makes thesecompounds useful as potential species for pharmaceutical applications orcandidates in the emerging chiral auxiliary field of asymmetric organicsynthesis. Given the potential uses, a cost efficient and simple processthat can synthesis derivatives from FDM and/or bHMTHFs would beappreciated by manufacturers of both industrial and specialty chemicalsalike as a way to better utilize biomass-derived carbon resources.

SUMMARY OF THE INVENTION

The present invention relates, in part, to a method of synthesizing andisolating dicarbamate derivatives of the reduction products of2-hydroxymethyl-5-furfural (HMF). The method involves providing amixture of HMF-reduction products with a cyanate salt in an inertorganic solvent, reacting the mixture with an acid having a pK_(a) lessthan or equal to about 3.7. The reduction product of HMF is at least oneof: a) furan-2,5-dimethanol (FDM) and b)(tetrahydrofuran-2,5-diyl)dimethanol (THF-diols). The acid is added tothe reaction mixture at a controlled rate of about 0.03-0.1stoichiometric equivalents per minute.

In another aspect, the present invention pertains to the dicarb. ates ofHMF-reduction products produced from the method.

In yet another aspect, the present invention pertains to processes formaking certain derivatized materials that contain the dicarbamates ofHMF-reduction products as structural precursors of non-polymercompounds, or as a monomer in either homopolymers or copolymers, and thederivative materials themselves.

DETAILED DESCRIPTION OF THE INVENTION SECTION I.—DEFINITION

As used herein the following definitions are applicable:

The term “monomer” refers to a repeating structural unit of a polymer. Amonomer typically is a lower molecular weight compound that can formcovalent chemical bonds with other monomers, resulting in a polymer.

The term “polymer” refers to a compound comprising repeating structuralunits (monomers) connected by covalent chemical bonds, and which mayinclude oligomers. Polymers may be derivatized (for example byhydrolysis), cross-linked, grafted, or end-capped. Non-limiting examplesof polymers may include homopolymers, non-homopolymers, blockcopolymers, terpolymers, tetra-polymers, and homologues. A polymer maybe a random, block, or an alternating polymer, or a polymer with mixedransom, block, and/or alternating structure.

The term “homopolymer” refers to a polymer composed of a single type ofrepeating structural unit (monomers).

The term non-homopolymer” refers to a polymer having more than one typeof repeating structural units (monomers).

The term “copolymer” refers to a non-homopolymer composed of two or moretypes of repeating structural units (monomers), such as a “terpolymer”or “tetra-polymer,” respectively, with three or four types of repeatingstructural units (monomers).

The term “derivative” refers to a material or chemical compound that isprepared as a secondary or tertiary reaction product from a primarystructural substituent (for non-polymer compounds), or a monomer orpolymer compound, in which the primary structural substituent, monomeror polymer has been modified in terms of either a functional group,structural moiety, or chemical linkage.

The term “water-tolerant Lewis acids” refers to a phenomenoloaicproperty of certain Lewis acid catalysts that are not deactivated by thepresence of water, contrary to conventional Lewis acids that aresummarily deactivated by reaction with water. Hence, a particular Lewisacid may show water tolerance for the purpose of one reaction, but nottoward another reaction. (See e.g., S. Kobayashi, S. Nagayama, & T.Busujima, “Lewis Acid Catalysts Stable in Water: Correlation BetweenCatalytic Activity in Water and Hydrolysis Constants and Exchange RateConstants for Substitution of Inner-Sphere Water Ligands,” J. Am, Chem.Soc., 120(32): 8287-8288 (1998); S. Kobayashi & I. Hachiya, “LanthanideInflates as Water-Tolerant Lewis Acids: Activation of CommercialFormaldehyde Solution and Use in the Aldol Reaction of Silyl Enol Etherswith Aldehydes in Aqueous Media,” The Journal of Organic Chemistry,59(13): 3590-3596, July 1994; N. A. Rebacz, “Hydration and Hydrolysiswith Water Tolerant Lewis Acid Catalysis in High Temperature Water,”PhD, Dissertation, University of Michigan (2011), the contents of whichare incorporated herein by reference.)

SECTION II.—DESCRIPTION

As biomass derived compounds that afford great potential as surrogatesfor non-renewable petrochemicals, FDM and bHMTHFs, the reductionproducts of HMF, are a class of bicyclic furanodiols that are valued asrenewable molecular entities. As referred to above, these reductionproducts of HMF are versatile chemical platforms that have recentlyreceived interest because of their aromatic character (FDM) andintrinsic chiral bi-functionalities (bHMTHFs), which can permit asignificant expansion of both existing and new derivative compounds thatcan be synthesized.

A.—Preparation of Dicarbamates of Reduction Products of HMF

The method for preparing dicarbamates of reduction products of HMF(i.e., FDM, THF-diols), as described herein, is a mild, high-yielding,single-step synthesis process. The process involves reacting a mixtureof a HMF-reduction product and a cyanate salt in an inert organicsolvent with an acid having a pK_(a) of about 3.7 or less.

The present synthesis process can result in yields of correspondingdicarbamates of FDM and bHMTHFs, as demonstrated in the accompanyingexamples. The process is able to produce corresponding dicarbmates inreasonably high molar yields of at least 55% from the reduction productsof HMF and cyanate starting materials, typically about 60% or 70% toabout 75% or 80%. With proper control of the reaction conditions andtime, one can achieve a yield of about 82%-95% or better of thedicarbamates.

The amount of cyanate salt used should be in excess of the amount ofHMF-reduction products. The range of cyanate to FDM or bHMTHF ratio interms of mole percent is a minimum of 2:1 (i.e., one cyanate per —OHgroup of a FDM or bHMTHF), and up to about 4:1 or 5:1 for purposes ofpracticality. (There is no theoretical maximum ratio, as once thereduction products of HMF forms the dicarbamate no further reactionswill occur. However, the more unreacted salts that is present in thereaction, the more concern one may have in removing the saltssubsequently during an aqueous wash.)

The reduction product of HMF is at least one of the following: FDM,bHMTHF, or a combination thereof The respective reduction products ofHMF can be obtained either commercially or synthesized from relativelyinexpensive, widely-available biologically-derived feedstocks.

The cationic counter-ion to the cyanate salt is at least one of thefollowing: Na, K, Li, Ag, Hg, Al, Ca, Mg, Pb, Sn, Ti, Ni, Cs, Rb, Cu,Zn, Cd, In, Co, Ga, Ba, Pd, Pt, Tl, Fr, Sb, Ge, Sr, Be, V, Bi, Mo, Mn,Fe, Nb, Cr, Eu, organic cations of ammonium, pyridinium, and/or acombination thereof.

The method uses a non-aqueous reaction system with an organic solventthat enables the reduction products of HMF to be soluble and reactivewith the acid. The organic solvent can be at least one of the following:methylene chloride, chloroform, carbon tetrachloride, benzene, toluene,xylenes, linear and/or branched alkanes, tetrahydrofuran, 1,4-dioxane,dimethylsulfoxide, acetonitrile, dimethylformamide, acetic acid, FIMPT,nitromethane, pyridine, N-methyl pyrolidinone, dimethylacetamide, ethylacetate, acetone, methyl tert-butyl ether, diethyl ether.

An acid that is miscible or soluble in the organic solvent and having apKa less than or equal to about 3.7 can be employed in the presentsynthesis. An acid having a pKa≦3.7 will have a greater propensity toprotonate the cyanate in situ to generate isosyanic acid, which is theactive electrophilic species. The acid preferably has pKa of about 3.5or less (e.g. about 2.5 or 2.7 to about 3.0 or 3.6; or about 2.6 or 2.8to about 3.2 or 3.3) as in some examples. The acid can be either a) anorganic acid orb) a mineral acid. Organic acids tend to have an enhancedsolubility in an organic solvent (e.g., methylene chloride) which maymake them more effective in the reaction; nevertheless, mineral acidscan be just as effective. An organic acid can be: e.g., trifluoro-aceticacid (TFA), trichloro-acetic acid, oxalic acid, pyruvic acid, malonicacid, furamic acid, maleic acid, malic acid, tartaric acid, picric acid,electron deficient benzoic acids (mono, di, and tri-nitro, cyano,trifluoro), terephthalic acid, methanesulfonic acid, p-toluenesulfonicacid and trifluoromethylsulfonic acid. A mineral acid can be: e.g.,sulfuric acid, hydrogen halides (HCl, HBr, HI), perchloric acid,phosphoric acid, and boric acid.

Introduction of the acid to the reaction system should be performed in astead and controlled manner so as to maximize production of the targetdicarbamate, while avoiding or minimizing the formation of undesiredside products. The acid is added to the reaction mixture of FDM orbHMTHFs at a rate of about 0.03-0.1 stoichiometric equivalents perminute. Acids with a pKa of 3.5 or greater should be added slowly,because of the exothermic nature of the reaction.

One can execute the synthesis reaction in a single vessel underrelatively mild conditions at a temperature of up to about 50° C. or 55°C. In general, the reaction is conducted at a starting temperature in arange from about 0° C. to about 30° C. or 40° C. More typically, theinitial reaction temperature is in a range from about 10° C. to about35° C. In certain embodiments, the reaction is performed at aboutambient room temperature (i.e., ˜18° C. to ˜25° C.) to about 20° C. or22° C. higher than room temperature. Because of its exothermic nature,the reaction can generate an additional 10° C.-15° C. of heat over andabove the initial reaction temperature. This phenomenon permits thereaction to proceed at lower initial temperatures.

An advantage of the present process is that in excess amounts ofcyanate, the reduction products of HMF converts substantially orcompletely to its dicarbamate species, minimizing waste and anyremaining amount of unreacted starting materials in the final productmixture that may need separation. Another advantage of the presentmethod is that the synthesis process requires minimal purification. Asthe dicarbamates are formed, they will precipitate from the homogeneousreaction mixture, and can be easily filtered to separate them fromsolution. One can further purify the FDM or bHMTHF dicarbamates using avariety of different techniques; for example, in a protocol thatinvolves simple filtration, washing, and drying under high vacuum.

The process is able to produce dicarbamates of the reduction products ofHMF in reasonably high molar yields of at least 55% from the bHMTHFstarting materials, up to near quantitative yields. Typically yieldsrange from about 60% to about 70%, or more typically about 68% or 75% toabout 80% or 83%. With proper control of the reaction conditions andtime, one can achieve a yield of about 85% to about 94% or 95% or betterof the dicarbamate, such as demonstrated in the accompanying examples.Schemes 3 and 4, respectively, illustrate the general structures of thedicarbamate species of FDM and bHMTHFs.

B.—Derivative Compounds of Dicarbamates of HMF-Reduction Products

Dicarbamates of HMF-reduction products can be useful and valuableprecursor chemical compounds for a variety of potential products,including for instance, a broad range of polymers (e.g., polyurethanes),chiral auxillaries (e.g., for asymmetic synthesis used in pharmaceuticalproduction), surfactants, or solvents. The present carbamate compoundscan be adapted to serve as either a new, bio-derived monomer or areplacement for existing structurally analogous compounds, such as usedin the pharmaceutical, personal care, or industrial chemical (derivedfrom fossil hydrocarbons) industries.

Some of the uses to which carbamates can be adapted are illustratedgenerally in the following list, which includes examples of carbamatesused as monomer units in various kinds of polymer compounds orcompositions: 1) U.S. 2004/0087728 A1 or U.S. 2005/0080196 (a curablesurface coating composition containing a carbamate functional additionpolymer); 2) U.S. 2013/0090443 (polymerization of carbamate andthiocarbamate compounds for cosmetic, skin or hair care, or otherpersonal care compositions); 3) U.S. 2002/0119320 or U.S. 2004/0236031(coating composition containing a carbamate-functional group or resin);4) U.S. Pat. No. 3,165,498 (polyfunctional interpolymers of olefinicallyunsaturated carbamates and olefins, which have a plurality of carbamategroups); or 5) U.S. 2012/0125800 (polymer with a polyester-carbamatebackbone and one or more blocked isocyanate groups and coatingcomposition).

Scheme 5, for example, presents several representative derivativecompounds that may be made from bHMTHF dicarbamates. Although only thecis-species are depicted in the derivative synthesis diagram, thepresent reactions encompass both the cis- and trans-bHMTHF dicarbamateanalog structures and derivative compounds, as well as similar reactionsto prepare such derivative compounds are also contemplated herein.

Proceeding clockwise, each of the example reactions (a-i) shown inScheme 5, can be executed respectively using, for instance, thefollowing reagents:

-   a) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((113-dichloranylidene)carbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis (methylene)    bis((113-dichloranylidene)carbamate): NaOCl, AcOH, H₂O;-   b) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis(methacryloylcarbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis(methacryloylcarbamate): Methacryloyl chloride, t-BuOK, THF;-   c) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((4-formylphenyl)carbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((4-formylphenyl)carbamate): p-bromobenzaldehyde, Cs₂CO₃,    Pd(OAc)₂, 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene, THF;-   d) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((2,2,2-trifluoroacetyl)carbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis (methylene)    bis((2,2,2-trifluoroacetyl)carbamate): Trifluoroacetic anhydride,    Et₂O;-   e) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis(tert-butylcarbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis(tert-butylcarbamate): 2-Methylpropene, BF₃-Et₂O, PhCH₃;-   f) for diethyl    N′,N″-(((((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))bis(oxy))bis(carbonyl))(1E,1′E)-diformimidate    and diethyl    N′,N″-(((((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))bis(oxy))-bis(carbonyl))(1E,1′E)-diformimidate:    Triethyl orthoformate, BF₃-THF, THF;-   g) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((oxo-λ⁴-sulfanylidene)carbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((oxo-λ⁴-sulfanylidene)carbamate): SOCl₂;-   h) for dimethyl (((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))    bis(carbonate) and dimethyl    (((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)) bis(carbonate):    Lewis acids (Bi(OTf)₃, Ga(OTf₃, Sc(OTf₃, In(OTf)₃, Cu(OTf)₃,    Al(OTf)₃, Lanthanide triflates, CH₃OH, ˜180-220° C.;-   i) for ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((diaminophosphoryl)carbamate) and    ((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)    bis((diaminophosphoryl)carbamate): 1) PCl₅, CHCl₃; 2) H₂O, 0° C.; 3)    NH₃, Et₃N, CHCl₃, reflux. The particular time and temperatures will    vary for each of the reaction processes, and can be determined    empirically.

Similarly, Scheme 6 illustrates several representative derivativecompounds that can be synthesized from FDM dicarbamate using the samereagents as listed above.

As before, preceding clockwise, each of the example reactions (a-i)shown in Scheme 6, can be prepared respectively using, for instance, thefollowing reagents:

-   a) for furan-2,5-diylbis(methylene)    bis((chloroimino)-13-chloranecarboxylate): NaOCl, AcOH, H₂O;-   b) for furan-2,5-diylbis(methylene) bis(methacryloylcarbamate):    Methacryloyl chloride, t-BuOK, THF;-   c) for furan-2,5-diylbis(methylene) bis((4-formylphenyl)carbamate):    p-bromobenzaldehyde, Cs₂CO₃, Pd(OAc)₂,    4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene, THF;-   d) for furan-2,5-diylbis(methylene)    bis((2,2,2-trifluoroacetyl)carbamate): Trifluoroacetic anhydride,    Et₂O;-   e) for furan-2,5-diylbis(methylene) bis(tert-butylcarbamate):    2-Methylpropene, BF₃-Et₂O, PhCH₃;-   f) for diethyl    N′,N″-(((furan-2,5-diylbis(methylene))bis(oxy))bis(carbonyl))(1E,1′E)-diformimidate:    Triethyl orthoformate, BF₃-THF, THF;-   g) for furan-2,5-diylbis(methylene)    bis((oxo-λ⁴-sulfanylidene)carbamate): SOCl₂;-   h) for furan-2,5-diylbis(methylene) dimethyl bis(carbonate): Lewis    acids (Bi(OTf)₃, Ga(OTf₃, Sc(OTf₃, In(OTf)₃, Cu(OTf)₃, Al(OTf)₃,    Lanthanide triflates, CH₃OH, ˜180-220° C.;-   i) for furan-2,5-diylbis(methylene)    bis((diaminophosphoryl)carbamate): 1) PCl₅, CHCl₃; 2) H₂O, 0° C.; 3)    NH₃, Et₃N, CHCl₃, reflux.

Another example of a derivative synthesis reaction that employs thedicarbamates of reduction products of HMF described herein is shown inScheme 7 and 8 (FDM and bHMTHF, respectively), which involves preparingformaldehyde polymers. (The reactions are expounded further in theaccompanying examples for derivative compounds in the Examples section,infra).

The formaldehyde-FDM and/or bHMTHF dicarbamate polymers would haveapplications (e.g., thermosetting resins) similar to, for instance, thatdescribed in U.S. 2009/0149608 (thermosetting resin composition withpolycarbamate and polycarbamides reacted with formaldehyde), or Moon G.Kim, “Renewable Polyol-based Polycarbamates andPolycarbamate-Formaldehyde Thermosetting Resins,” JOURNAL OF APPLIEDPOLYMER SCIENCE, 122(4), 2209-2220 (15 Jun. 2011), the contents of whichare incorporated herein by reference.

Another possible useful application for the present dicarbamates of thereduction products of HMF can be as a monomer in an analogous method forcrosslinking polyurethanes, such as described in U.S. 2011/0313091 (acrosslinked polyurethane composition having a polycarbamate as a firstcomponent and a polyaldehyde or acetal or hemi-acetal thereof as asecond component), the content of which is incorporated herein byreference.

Furthermore, N-acylated carbamates can be useful platforms in thesynthesis of biologically active compounds. The preparation and use ofthese derivative compounds are described, for example, by Liu, Xue-Kui,et al., ORGANIC & BIOMOLECULAR CHEMISTRY (2012), 10(6), 1275-1284;Kuhakam, Chutima et al., TETRAHEDRON LETTERS (2007), 48(46), 8182-8184;Brouillette, Wayne J. et al., JOURNAL OF ORGANIC CHEMISTRY (1979),44(5), 839-43, or in U.S. Pat. No. 3,819,683, relating to arylN-methyl-N-acylcarbamates, the contents of which are incorporated hereinby reference.

As an illustration of an alternative embodiment of a method for makingderivatives, Schemes 9 and 10, exhibits a general reaction for aLewis-acid-(LA)-triflate-mediated N-acylation of FDM or bHMTHFdicarbamates. Although Lewis acids have been employed for situationslike N-acylation (e.g., Reddy, Chada Raji, et al., ARCHIVE FOR ORGANICCHEMISTRY (ARKIVOC) 2008 (ii) 250-257), none have involvedwater-tolerant triflates and/or use a low quantity (≦1 or 2 mol. %)catalyst load (e.g., about 0.01 mol. % to about 1.5 mol. %) as in thepresent method and examples. In the present reactions, effectivecatalyst loads can range from as little as about 0.005 or 0.035 mol. %up to about 4 or 5 mol. %. Reaction times will tend to be longer withlower amounts, which can afford some degree of control in the reaction.

The Lewis-acid triflate is water-tolerant, and thus useful as ahomogeneous catalyst in an aqueous milieu. That is in other words, theLewis acid triflate exhibits a uniquely stable behavior in water, inthat it only very slowly hydrolyzes, and thus retains its acidity for aprotracted time period when in the presence of water. For example,aluminum triflate is a powerful Lewis acid in an aqueous environment;while in contrast, aluminum chloride will hydrolyze immediately forminghydroxyl groups, and lose all of its acidic capacity. It is believedthat a role of the Lewis-acid triflate is in lowering the activationbarrier of the acid chloride or anhydride by coordinating to thecarbonyl moiety. This action promotes a supervening displacement by themoderately nucleophilic FDM or bHMTHF dicarbamate to generate theN-acylated carbamate derivative compounds.

Schemes 11 and 12 illustrate particular examples of this reaction,involving N-acylation of carbamates of the HMF-reduction products withthe bio-based fatty acid, oleic acid.

The preparation of various derivative compounds according to this methodof reaction will be described more fully in the accompanying examplesbelow. Note that excess reagents will tend to generate undesired sidereactions under the conditions employed. Hence, the ratio of reagentsshould be kept in a range about 5:1 maximum ratio of formaldehyde to FDMor bHMTHF dicarbamate (Example 1, vide infra), or as in about 2:1 ratiofor reagent to FDM, bHMTHF dicarbamate (Examples 3 and 4, vide infra).The specific yield of derivative compounds will depend on the particularreactions. Typically, the yield of target derivative compound can rangefrom at least about 50% or 55% up to about 93% or 97% or better.

SECTION III.—EXAMPLES

The present invention is further illustrated with reference to thefollowing examples.

A. Dicarbamates Example 1 Synthesis of furan-2,5-diylbis(methylene)dicarbamate, B

Experimental: A two neck, 50 mL round bottomed flask was charged with 1g of FDM A (7.55 mmol), 1.97 g of sodium cyanate (30.2 mmol) and 20 mLof anhydrous methylene chloride resulting in a suspension. The neckswere then stoppered with rubber septa, one with a thermocouple insertthat immersed in the solution. While stirring, 2.32 mL oftrifluoroacetic acid was added via syringe dropwise over 5 minutes. Thetemperature of the solution warmed from 25° C. to 41° C. over 15 minutesand solids disappeared. After about 30 minutes, a white precipitateformed, which was filtered and analyzed as only byproduct sodiumtrifluoroacetate by ¹³C NMR (D₂O, 2000 scans) no residual FDM wasdescried). The supernatant was concentrated in vacuo, affording B as apale yellow solid that weighed 1.55 g (93% of theoretical). ¹³C NMR(CDCl₃, 100 MHz) δ (ppm) 151.61, 147.38, 113.57, 61.11 (notable FDMsignals at 154.27, 108.79, 57.76 ppm absent).

Example 2 Synthesis of ((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)dicarbamate and diastereomer, B

Experimental: A two neck, 50 mL round bottomed flask was charged with 1g of THF-diols A (9:1 cis/trans, 7.57 mmol), 1.97 g of sodium cyanate(30.2 mmol) and 20 mL of anhydrous methylene chloride resulting in asuspension. The necks were then stoppered with rubber septa, one with athermocouple insert that immersed in the solution. While stirring, 2.32mL of trifluoroacetic acid was added via syringe dropwise over 5minutes. The temperature of the solution warmed from 25° C. to 41° C.over 15 minutes and solids disappeared. After about 30 minutes, a whiteprecipitate formed, which was filtered, dried and determined to bebyproduct sodium trifluoroacetate by ¹³C NMR (D₂O, 2000 scans) noresidual FDM was espied). The supernatant was concentrated in vacuo,affording B as a loose, clear oil that weighed 1.42 g (86% oftheoretical). ¹³C NMR (CDCl₃, 100 MHz) δ (ppm) 157.39, 77.79, 69.37,27.45 (characteristic THF-Diol (meso, cis) signals at 80.46, 64.94,27.67 ppm absent)

B. Derivatives Compounds:

I. Derivatives of bHMTHFs Dicarbamates

Example 1 Synthesis of bHMTHF (9:1 cis/trans) Dicarbamate-FormaldehydePolymers

Experimental: A single neck, 50 mL round bottomed flask equipped with a½″ PTFE coated magnetic stir bar was charged with 300 mg of a 50%solution of formaldehyde (5 mmol), 219 mg of bHMTHF dicarbamates (9:1cis/trans, 1 mmol), 500 mL of water, and 1 N aqueous KOH until the pHwas 8.5. While stirring, the resultant suspension was heated to 85° C.;after 45 min, the solution opacity disappeared, and the reactioncontinued for 30 more min. After this time, the pH was adjusted to 1.5with 1N HCl and reaction proceeded until a viscosity change wasapparent, at which time the reaction was culminated by cooling and pHadjusting to 8 with 1N KOH. Here the residual solids are measured.

Example 2 Synthesis of (tetrahydrofuran-2,5-diyl)bis(methylene)bis(acetylcarbamate), 9:1 mixture of cis and trans diastereomers

Experimental: A 10 mL round bottomed flask equipped with a ¼″ PTFEcoated magnetic stir bar was charged with 250 mg of bHMTHF dicarbamatesA (9:1 cis/trans, 1.14 mmol), 56 μg of Sc(OTO₃ (0.1 mol %) and 2 mL ofanhydrous THF. While stirring, 251 μL of acetic anhydride (2.51 mmol)was added dropwise over 15 minutes. The solution was observed to warmconsiderably with each drop. After the entire volume had been added, themixture continued to stir at room temperature for an additional 5 hours.An aliquot was removed and spotted on a normal phase TLC plate, whichrevealed overlapping bands (cerium molybdate illumination, Rf=0.44,0.45) after development in 100% EtOAc. The signature bands correspondingto the 9:1 cis/trans mixture of A, Rf=0.29, 0.30 were noticeably absent,indicating full conversion of these starting materials. Solids were thenfiltered and excess solvent was then evaporated under reduced pressure,affording 321 mg (93% of theory) of B as a colorless oil, that analyzedby ¹³C NMR (100 MHz, d⁶-DMSO) as δ (ppm) 170.0, 169.4 152.8, 152.5,82.0, 81.6, 74.5, 67.2, 66.9, 30.5, 30.2, 24.1, 23.9 ppm.

Example 3 Synthesis of (tetrahydrofuran-2,5-diyl)bis(methylene)bis(benzoylcarbamate), 9:1 mixture of cis and trans diastereomers

Experimental: A 10 mL round bottomed flask equipped with a ¼″ PTFEcoated magnetic stir bar was charged with 250 mg of bHMTHF dicarbamatesA (9:1 cis/trans 1.14 mmol), 75 μg of Bi(OTf)₃ (0.1 mol %) and 2 mL ofanhydrous THF. While stirring, 291 μL of benzoyl chloride (2.51 mmol)was added dropwise over 15 minutes. The solution was observed to warmconsiderably with each drop. After the entire volume had been added, themixture continued to stir at room temperature for an additional 5 hours.An aliquot was removed and spotted on a normal phase TLC plate, whichrevealed two overlapping bands (UV-Vis illumination, Rf=0.50, 0.51)after development in 100% EtOAc. The signature bands corresponding to A,Rf=0.29, 0.30 were noticeably absent, adducing that A had fullyconverted. Solids were then filtered and excess solvent was thenevaporated under reduced pressure, affording 366 mg (86% of theoretical)of a B as a colorless oil, analyzed by ¹³C NMR (100 MHz, d⁶-DMSO) δ(ppm) 155.5, 155.3, 139.1, 138.8, 129.5, 129.2, 127.4, 127.2, 123.2,123.0, 85.6, 85.2, 67.8, 67.5, 30.7, 30.5 ppm.

Example 4 Synthesis of (tetrahydrofuran-2,5-diyl)bis(methylene)bis(acryloylcarbamate), 9:1 mixture of cis and trans diastereomers

Experimental: A 10 mL round bottomed flask equipped with a ¼″ PTFEcoated magnetic stir bar was charged with 250 mg of bHMTHF dicarbamatesA (9:1 cis/trans 1.14 mmol), 64 μg of In(OTO₃ (0.1 mol %) and 2 mL ofanhydrous THF. While stirring, 204 μL of propenoyl chloride (2.51 mmol)was carefully added, dropwise over 15 minutes. The solution was observedto warm considerably with each drop. After the entire volume had beenadded, the mixture continued to stir at room temperature for anadditional 6 hours. An aliquot was removed and spotted on a normal phaseTLC plate, which revealed two overlapping bands (cerium molybdateillumination, Rf=0.46, 0.47) after development in 100% EtOAc. Thesignature bands corresponding to A, Rf=0.29, 0.30 were noticeablyabsent, adducing that A had fully converted. Solids were then filteredand excess solvent was then evaporated under reduced pressure, affording338 mg (90% of theoretical) of B a colorless oil, analyzed by ¹³C NMR(100 MHz, d⁶-DMSO) δ (ppm) 170.2, 170.0, 153.4, 153.1, 132.5, 132.4,128.3, 128.0, 84.1, 83.9, 66.9, 66.6, 28.7, 28.4 ppm.

II. Derivatives of FDM Dicarbamates Example 1 Synthesis of FDMDicarbamate-Formaldehyde Polymers

Experimental: A single neck, 50 mL round bottomed flask equipped with a½″ PTFE coated magnetic stir bar was charged with 300 mg of a 50%solution of formaldehyde (5 mmol), 214 mg of bHMTHF dicarbamates (1mmol), 500 mL of water, and 1 N aqueous KOH until the pH was 8.5. Whilestirring, the resultant suspension was heated to 85° C.; after 45 min,the solution opacity disappeared, and the reaction continued for 30 moremin. After this time, the pH was adjusted to 1.5 with 1N HCl andreaction proceeded until a viscosity change was apparent, at which timethe reaction was culminated by cooling and pH adjusting to 8 with 1NKOH. Here the residual solids are measured.

Example 2 Synthesis of furan-2,5-diylbis(methylene) bis(acetylcarbamate)

Experimental: A 10 mL round bottomed flask equipped with a ¼″ PTFEcoated magnetic stir bar was charged with 250 mg of FDM dicarbamates A(9:1 cis/trans, 1.17 mmol), 58 μg of Sc(OTO₃ (0.1 mol %) and 2 mL ofanhydrous THF. While stirring, 257 μL of acetic anhydride (2.58 mmol)was added dropwise over 15 minutes. The solution was observed to warmconsiderably with each drop. After the entire volume had been added, themixture continued to stir at room temperature for an additional 5 hours.An aliquot was removed and spotted on a normal phase TLC plate, whichrevealed a single band (cerium molybdate illumination, Rf=0.42) afterdevelopment in 100% EtOAc. The signature band corresponding to theFDM-dicarbamate A Rf=0.27 was noticeably absent, indicating fullconversion of these starting materials. Solids were then filtered andexcess solvent was then evaporated under reduced pressure, affording 315mg (91% of theory) of B as a white solid material that analyzed by ¹³CNMR (100 MHz, d⁶-DMSO) as δ (ppm) 170.5, 153.1, 140.3, 109.2, 57.0,22.9.

Example 3 Synthesis of furan-2,5-diylbis(methylene)bis(benzoylcarbamate)

Experimental: A 10 mL round bottomed flask equipped with a ¼″ PTFEcoated magnetic stir bar was charged with 250 mg of bHMTHF dicarbamatesA (9:1 cis/trans 1.17 mmol), 79 μg of Bi(OTf)₃ (0.1 mol %) and 2 mL ofanhydrous THF. While stirring, 300 μL of benzoyl chloride (2.58 mmol)was added dropwise over 15 minutes. The solution was observed to warmconsiderably with each drop. After the entire volume had been added, themixture continued to stir at room temperature for an additional 5 hours.An aliquot was removed and spotted on a normal phase TLC plate, whichrevealed a single band (UV-Vis illumination, Rf=0.46) after developmentin 100% EtOAc. The signature bands corresponding to A, Rf=0.27 wasnoticeably absent, adducing that A had fully converted. Solids were thenfiltered and excess solvent was then evaporated under reduced pressure,affording 381 mg (89% of theoretical) of B as a light yellow solid,analyzed by ¹³C NMR (100 MHz, d⁶-DMSO) δ (ppm) 155.2, 141.6, 139.7,129.6, 129.1, 122.7, 108.3, 58.0.

Example 4 Synthesis of furan-2,5-diylbis(methylene)bis(acryloylcarbamate)

Experimental: A 10 mL round bottomed flask equipped with a ¼″ PTFEcoated magnetic stir bar was charged with 250 mg of FDM dicarbamates A(1.17 mmol), 70 ug of In(OTf)₃ (0.1 mol %) and 2 mL of anhydrous THF.While stirring, 212 μL of propenoyl chloride (2.58 mmol) was carefullyadded, dropwise over 15 minutes. The solution was observed to warmconsiderably with each drop. After the entire volume had been added, themixture continued to stir at room temperature for an additional 6 hours.An aliquot was removed and spotted on a normal phase TLC plate, whichrevealed a single band (cerium molybdate illumination, Rf=0.43) afterdevelopment in 100% EtOAc. The signature band corresponding to A,Rf=0.27 was noticeably absent adducing that A had fully converted.Solids were then filtered and excess solvent was then evaporated underreduced pressure, affording 346 mg (92% of theoretical) of B as a whitesolid, analyzed by ¹³C NMR (100 MHz, d⁶-DMSO) δ (ppm) 170.2, 153.0,141.2, 132.6, 127.3, 107.9, 57.0.

Although the present invention has been described generally and by wayof examples, it is understood by those persons skilled in the art thatthe invention is not necessarily limited to the embodiments specificallydisclosed, and that modifications and variations can be made withoutdeparting from the spirit and scope of the invention. Thus, unlesschanges otherwise depart from the scope of the invention as defined bythe following claims, they should be construed as included herein.

We claim:
 1. A precursor chemical compound comprising at least one ofthe following:


2. A chemical compound derived from at least one of the precursorchemical compounds according to claim 1, said derived chemical compoundis a polymer containing said precursor chemical compound as asubstituent.
 3. The derived chemical compound according to claim 2,wherein said polymer is a homopolymer with a structure:


4. A method of preparing a derivative chemical compound from at leastone of the precursor chemical compounds according to claim 13,comprising performing a Lewis-acid-(LA)-triflate-mediated N-acylation ofreduction products of HMF, according to:


5. The method according to claim 4, wherein said Lewis acid triflate iswater-tolerant.
 6. The method according to claim 4, wherein saidderivative chemical compound is at least one of the following forbHMTHF:

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((113-dichloranylidene)carbamate)

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((113-dichloranylidene)carbamate

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis(methacryloylcarbamate)

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis(methacryloylcarbamate)

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((4-formylphenyl)carbamate)

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((4-formylphenyl)carbamate)

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((2,2,2-trifluoroacetyl)carbamate

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((2,2,2-trifluoroacetyl)carbamate)

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis(tert-butylcarbamate)

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis(tert-butylcarbamate)

diethylN′,N″-(((((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))bis(oxy))bis(carbonyl))(1E,1′E)-diformimidate

diethylN′,N″-(((((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))bis(oxy))bis(carbonyl))(1E,1′E)-diformimidate

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((oxo-λ⁴-sulfanylidene)carbamate)

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((oxo-λ⁴-sulfanylidene)carbamate)

dimethyl (((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))bis(carbonate)

dimethyl (((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene))bis(carbonate)

((2R,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((diaminophosphoryl)carbamate)

((2S,5S)-tetrahydrofuran-2,5-diyl)bis(methylene)bis((diaminophosphoryl)carbamate)
 7. The method according to claim 4,wherein said derivative chemical compound is at least one of thefollowing for FDM:

furan-2,5-diylbis(methylene) bis((chloroimino)-13-chloranecarboxylate)

furan-2,5-diylbis(methylene) bis(methacryloylcarbamate)

furan-2,5-diylbis(methylene) bis((4-formylphenyl)carbamate)

furan-2,5-diylbis(methylene) bis((2,2,2-trifluoroacetyl)carbamate)

furan-2,5-diylbis(methylene) bis(tert-butylcarbamate)

diethylN′,N″-(((furan-2,5-diylbis(methylene))bis(oxy))bis(carbonyl))(1E,1′E)-diformimidate

furan-2,5-diylbis(methylene) bis((oxo-λ⁴-sulfanylidene)carbamate)

furan-2,5-diylbis(methylene) dimethyl bis(carbonate)

furan-2,5-diylbis(methylene) bis((diaminophosphoryl)carbamate)